True to its name, attention-deficit hyperactivity disorder (ADHD) has had a tough time garnering much notice from behavioural geneticists. The condition is highly heritable, but genetic association studies of ADHD, which affects about 2% of children, have mostly come up blank – until now.
A team led by Nigel Williams and Anita Thapar at Cardiff University School of Medicine in the UK have just linked the condition to large missing and extra chunks of chromosomal DNA known copy number variants (CNVs). “It gives us the first genetic link to ADHD,” Thapar said at a press briefing this morning.
Her team scanned the genomes of 410 children from Wales and northern England with ADHD and 1156 adults who were part of a large cohort study, looking for chunks of DNA 500,000 letters or longer that were either deleted or duplicated. They also limited their scan to rare CNVs, found in less than 1% of the general population.
On average, the children with ADHD were about twice as likely to possess such a mutation, compared to controls. Those children with an IQ below 70 were even likelier to have a swath of their genomes missing or duplicated.
CNVs have also been linked to autism and schizophrenia , and the results from the new study turn up some of the same chromosomal regions as those studies, such as a patch of chromosome 16 that is prone to duplication. Williams and Thapar’s team says this overlap could suggest a shared biological basis for autism and ADHD.
For the most part, however, it’s difficult to determine how the CNVs Thapar and Williams’ team identified are related to ADHD. Most of the insertions and deletions contain a number of genes, some implicated in brain function, some not.
Stephen Scherer, a medical geneticist at the Hospital for Sick Children in Toronto, Canada, expects that some of the CNVs will almost certainly play a causative role in an individual’s ADHD. An easy way to tell, he says, is to identify so-called de novo, mutations found in children with ADHD, but not their parents. In an analysis limited to a subset of their participants, Thapar and Williams identified four such mutations, including one on chromosome 16.
Like most genetic associations, the clinical applications of new study are years off and not obvious. “Williams and colleagues results are exciting, but how these findings will be clinically translated is still speculative,” writes J. Peter Burbach, in an editorial that accompanies the paper, which both appear in the journal Lancet. At a London press briefing, Thapar batted down question after question on the real-world application of her team’s work – but for one.
She hopes her team’s study will dispel the popular perception that ADHD results from poor parenting. “Finding this direct genetic link to ADHD should help clear this misunderstanding and address this issue of stigma,” she said.
Image: photo by tonx via Flickr under Creative Commons.